Controllable Synthesis Of Dihydrofuranyl Alcohols By Michael Addition Cyclization Of α,β-unsaturated Epoxides

2,3-dihydrofuran and its derivatives are a class of important organic compounds,and their related structures are widely distributed in natural products,and are important intermediates in organic synthesis and important components of many drugs.Drugs modified with 2,3-dihydrofuran structure have high biological activity,so they play a crucial role in medicine and biology.Michael addition reaction,as one of the classical personal reactions,is often used in drug synthesis and scientific research.In this thesis,through the design of the structure of the raw material,we developed a domino tandem rearrangement reaction triggered by the Michael addition reaction of the nucleophile and the raw material,and successfully synthesized 93 2,3-dihydrofuran alcohols by this reaction.1.Michael addition induced tandem synthesis of dihydrofuranol.Utilizing trans α,β-Preparation of epoxy acetaldehyde by epoxidation of unsaturated aldehydes,using different phosphorus ylid reagents to undergo Wittig reaction with epoxy acetaldehyde to obtain raw materials α,β-Unsaturated Epoxide.The experiment first optimized the conditions,followed by a universal experiment on the reaction,and proposed possible mechanisms for such reactions.The results showed that the optimal yield was achieved when DMF was used as the solvent and potassium carbonate was used as the base,and the reaction was carried out at55 ℃ for 3 hours.The raw materials have good applicability to Aromatic hydrocarbon and aliphatic hydrocarbon type substrates,carbon ring and heterocyclic substrates,electron donor and electron acceptor substituents,large and small steric hindrance substituents.β-Ketone ester compounds form nucleophilic anions under the action of carbonates,and then undergo Addition reaction with raw materials,followed by proton transfer under the action of water and bicarbonate ions,and then the oxygen anion formed by alkenation transformation reacts with epoxy groups,finally forming the framework structure of dihydrofuran through ring closing.2.Synthesis of dihydrofuranyl acetate from α,β-unsaturated epoxides.A new method to synthesize the structure of dihydrofuran was obtained by using β-diketones as reagents and α,β-unsaturated epoxides in Michael addition reaction.The solvent,temperature,alkali and catalyst were screened in the experiment.It was found that the yield of raw materials and reagents under the catalysis of DMSO,potassium carbonate and TBHAS at 70℃ for 2 hours could reach 80%.Then the expansion of the substrate was carried out.Large and small hindrance,symmetric and asymmetric reagents have good applicability.Finally,the possible mechanism of this kind of reaction is proposed.β-diketone compounds form nucleophilic anion under the action of carbonate,and after Michael addition with raw materials,they first undergo aldol condensation reaction to form a quaternary ring intermediate,and then split β-diketone through reverse aldol condensation reaction,and then proton transfer,and finally enolize the oxygen anion to react with epoxy groups to obtain another compound with a dihydrofuran framework structure.3.Mechanism of α-β-unsaturated epoxides quaternary ring reaction.The reaction of β-dione with α,β-unsaturated epoxides has been further studied.There are two reaction pathways in the intermediates obtained by Michael addition of reagents and raw materials: one is formed by intramolecular Aldol reaction to form quaternary ring intermediates,C-C bond is broken by intramolecular reverse Aldol reaction,and potassium carbonate and water assist in proton exchange,which is transformed by enolation,cyclization and transesternization to obtain dihydrofuran skeleton structure compounds;In the other,potassium carbonate and water assist proton exchange,enolization and cyclization reaction to obtain dihydrofuran derivatives,dihydrofuran derivatives undergo olactone exchange reaction to produce dihydrofuran skeleton structure compounds.